The fat controller: adipocyte development

Abstract

Obesity is a condition characterized by excess adipose tissue that results from positive energy balance and is the most common metabolic disorder in the industrialized world. The obesity epidemic shows no sign of slowing, and it is increasingly a global problem. Serious clinical problems associated with obesity include an increased risk for type 2 diabetes, atherosclerosis, and cancer. Hence, understanding the origin and development of adipocytes and adipose tissue will be critical to the analysis and treatment of metabolic diseases. Historically, albeit incorrectly, adipocytes were thought to be inert cells whose singular function was lipid storage. It is now known that adipocytes have other critical functions; the most important include sensitivity to insulin and the ability to produce and secrete adipocyte-specific endocrine hormones that regulate energy homeostasis in other tissues. Today, adipocytes are recognized as critical regulators of whole-body metabolism and known to be involved in the pathogenesis of a variety of metabolic diseases. All cells come from other cells and many cells arise from precursor cells. Adipocytes are not created from other adipocytes, but they arise from precursor cells. In the last two decades, scientists have discovered the function of many proteins that influence the ability of precursor cells to become adipocytes. If the expansion of the adipose tissue is the problem, it seems logical that adipocyte development inhibitors could be a viable anti-obesity therapeutic. However, factors that block adipocyte development and limit adipocyte expansion also impair metabolic health. This notion may be counterintuitive, but several lines of evidence support the idea that blocking adipocyte development is unhealthy. For this reason it is clear that we need a better understanding of adipocyte development.

Figure 1. Zfp521 is novel modulator of adipocyte commitment and differentiation.

Many transcription factors are induced during adipocyte differentiation. Some of these, like members of the AP-1 family, are induced early during adipocyte development. Other transcription factors like PPARγ promote adipocyte differentiation. Adipocyte development is also influenced by several transcription factor families that have negative effectors on adipogenesis. Zfp521 is a novel modulator of adipocyte development that mediates its inhibitory effects on adipocyte development by regulating the activity of two other transcription factors, Zfp423 and Ebf1.